The major objectives of this research project include correlation of the biochemical structure and physical-chemical characteristics of polypeptide hormones of the placenta and pituitary with their biologic and immunologic properties and investigation of factors regulating the biosynthesis, storage, and secretion of the hormones from normal and abnormal endocrine cells. The project was initiated with a detailed analysis of the chemistry of the polypeptide hormone human placental lactogen (hPL), a protein hormone closely related to human pituitary growth hormone and prolactin. In earlier work, we established the amino acid sequence of hPL, identified its homology at 86% of the residues with growth hormone and initiated efforts to correlate the biologic and immunologic properties of hPL and growth hormones. Further developments included the characterization of derivatives produced by chemical and enzymatic methods with attempts to identify specific sites of biologic activity in each molecule. Recent findings include the identification in extracts of human placenta and in the blood of pregnant women of a large form of hPL which is quite similar to large forms of growth hormone and prolactin in the blood and pituitary gland. Chemical studies showed that this larger form of hPL was a disulfide dimer of the native molecule. From biosynthetic studies, the generation and significance of larger forms of hPL, growth hormone and prolactin in relation to normal and abnormal synthetic and secretory processes of the placenta and pituitary will also be established. These studies will be extended, with particular emphasis on identifying dimeric hPL in patients with malignant disorders. These studies will provide further information on the homologies that exist in the biochemistry and physiology of placental and pituitary hormones.